In situ decellularization of a large animal saccular aneurysm model: sustained inflammation and active aneurysm wall remodeling
Authors
King, Robert M.Caroff, Jildaz
Langan, Erin T.
Leporati, Anita M.
Rodriguez-Rodriguez, Aurora
Raskett, Christopher M.
Gupta, Suresh
Puri, Ajit S.
Caravan, Peter
Gounis, Matthew J.
Bogdanov, Alexei A. Jr.
UMass Chan Affiliations
Department of Radiology, Laboratory of Molecular Imaging ProbesDepartment of Radiology, New England Center for Stroke Research
Document Type
Journal ArticlePublication Date
2020-10-05
Metadata
Show full item recordAbstract
OBJECTIVE: To investigate in situ decellularization of a large animal model of saccular aneurysm as a strategy for achieving aneurysmal growth and lasting inflammation. METHODS: 18 New Zealand White rabbits were randomized 2:1 to receive endoluminal sodium dodecyl sulfate infusion (SDS, 1% solution, 45 min) following elastase or elastase-only treatment (control). All aneurysms were measured by digital subtraction angiography every 2 weeks. Every 2 weeks, three of the rabbits (two elastase + SDS, one control) underwent MRI, followed by contrast injection with myeloperoxidase (MPO)-sensing contrast agent. MRI was repeated 3 hours after contrast injection and the enhancement ratio (ER) was calculated. Following MRI, aneurysms were explanted and subjected to immunohistopathology. RESULTS: During follow-up MRI, the average ER for SDS-treated animals was 1.63+/-0.20, compared with 1.01+/-0.06 for controls (p < 0.001). The width of SDS-treated aneurysms increased significantly in comparison with the elastase aneurysms (47% vs 20%, p < 0.001). Image analysis of thin sections showed infiltration of MPO-positive cells in decellularized aneurysms and surroundings through the 12-week observation period while control tissue had 5-6 times fewer cells present 2 weeks after aneurysm creation. Immunohistochemistry demonstrated the presence of MPO-positive cells surrounding decellularized lesions at early time points. MPO-positive cells were found in the adventitia and in the thrombi adherent to the aneurysm wall at later time points. CONCLUSIONS: In situ decellularization of a large animal model of saccular aneurysms reproduces features of unstable aneurysms, such as chronic inflammation (up to 12 weeks) and active aneurysm wall remodeling, leading to continued growth over 8 weeks.Source
King RM, Caroff J, Langan ET, Leporati A, Rodriguez-Rodriguez A, Raskett CM, Gupta S, Puri AS, Caravan P, Gounis MJ, Bogdanov AA Jr. In situ decellularization of a large animal saccular aneurysm model: sustained inflammation and active aneurysm wall remodeling. J Neurointerv Surg. 2020 Oct 5:neurintsurg-2020-016589. doi: 10.1136/neurintsurg-2020-016589. Epub ahead of print. PMID: 33020207. Link to article on publisher's site
DOI
10.1136/neurintsurg-2020-016589Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48477PubMed ID
33020207Related Resources
ae974a485f413a2113503eed53cd6c53
10.1136/neurintsurg-2020-016589